Thioether compounds are useful in many industries including those related to pharmaceuticals, agricultural chemicals, dyestuffs, and color photography. In color photography using silver halide-based light sensitive materials, a color image is obtained by the reaction of a color image forming coupler with the oxidation product of a color developing agent. The oxidized developer is formed upon development of exposed silver halide granules present in a gelatin emulsion layer which also contains the color image forming coupler. The two react to generate the dye of which the color image is formed. The color image forming materials (couplers) possess a site that is activated toward reaction with oxidized developer (the coupling site). It is common for couplers to possess a leaving group (coupling-off group) at the activated site. Couplers with such a structure allow for the theoretical use of only two moles of silver halide to generate one mole of dye and are thus called two equivalent couplers. Couplers without a coupling-off group are termed four equivalent couplers since theoretically four moles of silver must be used to obtain one mole of image-forming dye. In practice, the reactions are far less efficient, and much more than two or four equivalents is needed to achieve the desired degree of dye formation in either instance. The coupling-off group itself, which may be a photographically useful group (PUG), may serve a function such as carrying out color correction, assisting in the bleaching of unwanted silver, contributing to sharpness, or otherwise providing interimage effects. Another class of compounds that couple with oxidized developer to release photographically useful groups are those which form either colorless species or dyes that are not retained in the final image (U.S. Pat. No. 5,151,343) sometimes referred to as "universal" couplers. Thiol coupling off groups have been employed for all the above purposes and couplers which release them are valuable tools for obtaining desirable features in a photographic system. (U.S. Pat. Nos. 4,556,630 and 4,853,319)
A variety of methods exist for preparation of these thioether materials. The most widely used process is arylthiolation, and it consists of reacting a coupler which contains one or two hydrogens at the coupling site (a four equivalent coupler) with an activated derivative of the thiol which has been preformed in a separate step. The most common derivatives are sulfenyl halides 1, which are formed as described in U.S. Pat. No. 4,853,319 and U.S. Pat. No. 4,556,630 by reaction of either a thiol or a disulfide with a halogenating agent in a polar solvent such as dimethylformamide. Derivatives such as sulfenic acid amides 2, (U.S. Pat. No. 4,855,441), thiosulfonyl compounds 3, (DE 3,624,103), S(alkyl or arylthiol)isothioureas 4, (U.S. Pat. No. 4,293,691), thiuramdisulfides, thiocarbonyldisulfides and carbonyldisulfides 5, (U.S. Pat. No. 4,032,346) have also been described.
Thus, there have been employed the following thiolating reagents: ##STR1##
The sulfenyl halide method involves either formation of the sulfenyl halide in a separate step by addition of bromine, gaseous chlorine or a halogenating agent such as sulfuryl chloride to a disulfide or thiol in a polar solvent such as dimethylformamide followed by addition of the four equivalent coupler, or by introducing the halogenating agent into a mixture of the two reactants. There are numerous drawbacks to this method.
For example, the extent of sulfenyl halide formation cannot be ascertained with certainty. No good in-process assay is available for such a material, and it must be assumed that the reaction has gone to completion based on the amount of halogenating agent added. This can lead to yield and quality variations. Furthermore, halogenated impurities are generated by the side-reaction of the starting materials and products with free halide ions and radicals. These side-reaction products are undesirable and must be removed by a separate purification step. This results in lower yields and higher costs associated with an extra step and gives rise to the further problem of disposal of waste liquors.
As added disadvantages, it is noted that corrosive and difficult to handle reagents such as brominating reagents, are employed and that the process is not environmentally benign. High waste volumes are generated because of the need for extra purification and the halogenated wastes cannot be recycled in accordance with environmental regulations. They must be incinerated which increases costs and poses enough of an environmental threat to make production of large volumes of material via this route undesirable.
The other types of derivatives, 2-5, which have been described also must be prepared in a separate step. 2 and 3 are made through the intermediacy of the sulfenyl halide and therefore suffer from the aforementioned limitations regarding halogenation. Reagents 4 and 5 are both disadvantageous in their methods of preparation. The derivative 4 is prepared by oxidation of the thiol component in the presence of a thiourea with hydrogen peroxide. 5 is made by oxidation of the corresponding mercaptan with an appropriate oxidant as described in U.S. Pat. No. 4,032,346 and is not useful for introduction of simple alkyl or aryl thiol substituants. All these derivatives must be used in at least a 1:1 molar ratio with the four equivalent coupler and one half of the disulfide entity functions purely as a leaving group which does not react to form desired product. Half the reactant must therefore be separated from the final product and disposed of. Thus, the efficiency of this process is, at most, 50% based on the disulfide reactant. Any strategy which employs one of these derivatives is costly due to the great number of steps involved, the lower throughput resulting from higher molecular weight intermediates, the amount of waste generated, and the molar stoichiometry required for complete product formation.
DD 295,364 appears to describe a reaction between diheterocyclic disulfides and active methylene compounds in acetic acid to provide heterocyclic thioethers. The reported yields are too low to be of commercial value. DE 3624 103 describes preparation of arylthiol pyrazalone couplers via reaction of the halogenated coupler parent with the anion of the desired thiol. U.S. Pat. No. 5,104,994 covers preparation of thiopyrazoles by two methods: 1) substitution of an amino substituent for a thio substituent by diazotization with butyl nitrite in the presence of a disulfide, and 2) reaction of the lithium salt of a pyrazole with a molar equivalent of a disulfide at low temperature. The lithiated pyrazole is pre-formed by halogen metal exchange of a bromo pyrazole with n-butyl lithium at low temperature. Practically, it would be very difficult to successfully carry out this reaction on a production scale basis.
Several other thiolation methods have been reported for active methylene compounds but they appear to be limited in scope and/or are not adaptable to large scale manufacture. The method of Otto et.al. (Arch. Pharmaz., 304, pp 504-506 (1971)), in which thiols are heated with pyrazalones in dimethylsulfoxide, has been reported to provide 4arylthio pyrazalones. The practicality of this method is limited to laboratory scale preparations because the excessively high reaction temperature (near 200.degree. C.) would present a safety hazard in a large scale facility. The isolation of the products would require large wash volumes which would then have to be disposed of. When it was attempted to modify the conditions to those that would be safe and practical for commercial manufacture, it was found that the reaction did not proceed to completion at lower temperatures in the absence of a base. The method described was not extended to other couplers or other compounds containing active methylene or conjugated to such active compounds. Runge et.al. (Sulfur Letters, 12, (1+2), pp 33-44, (1990)) describes organothiolation of active methylene compounds in the presence of carbon tetrachloride and base. However, the presence of reactive halogen species in the mixture could lead to the same halogenated impurities produced by the sulfenyl halide method. These can produce undesirable effects if present in the final coupler. There are hazards associated with the use of a known carcinogen such as carbon tetrachloride and special precautions would have to be taken to use it commercially. Non-recoverable waste and disposal of halogenated liquors are deterents to the use of this method. In addition, no disclosure of it's application to photographically useful compounds is made.
In particular, what is needed is a process that uses reagents that are free from reactive halogen so that no unwanted halogenation of the reactants or products can take place to form undesirable halogenated impurities which contaminate the desired product, and so that there are no environmentally hazardous halogenated wastes which must be disposed of and no unsafe halogenated compounds to be handled.
In summary, there is a need for a more efficient, safer, and more environmentally favorable method for the manufacture of thioether-containing compounds.